Clinical Challenges and Consequences of Measurable Residual Disease in Non-APL Acute Myeloid Leukemia

Abstract

The ability to detect residual levels of leukemic blasts (measurable residual disease, MRD) has already been integrated in the daily routine for treatment of patients with chronic myeloid and acute lymphoblastic leukemia. In acute myeloid leukemia (AML), a variety of mostly retrospective studies have shown that individuals in AML remission who tested positive for MRD at specific time-points or had increasing MRD levels are at significantly higher risk of relapse and death compared to MRD-negative patients. However, these studies differ with respect to the “MRD-target”, time-point of MRD determination, material analyzed, and method applied. How this probably very valuable MRD information in individual patients may be adapted in the daily clinical routine, e.g., to separate patients who need more aggressive therapies from those who may be spared additional—potentially toxic—therapies is still a work-in-progress. With the exception of MRD assessment in acute promyelocytic leukemia (APL), the lack of randomized, prospective trials renders MRD-based decisions and clinical implications in AML a difficult task. As of today, we still do not have proof that early intervention in MRD-positive AML patients would improve outcomes, although this is very likely. In this article, we review the current knowledge on non-APL AML MRD assessment and possible clinical consequences.

Molecular Monitoring in Acute Myeloid Leukemia Patients Undergoing Matched Unrelated Donor – Hematopoietic Stem Cell Transplantation: Single Center Experience

“…Regarding the pre-transplant MRD assessment in AML the prognostic significance of MRD status is still uncertain and the time points for MRD assessment are not precisely defined. According to some published data in NPM1-mutated AML [5,12,13,14] estimating the dynamics of MRD loads can be very indicative for the treatment response. However, there is insufficient data on the predicative significance of pre-transplant MRD in other AML molecular subtypes.…”

MRD Tailored Therapy in AML: What We Have Learned So Far

“…The technique is accessible and widely applicable for about 90% of the AML patients ( 4 ). However, a high level of expertise is needed to perform MFC-MRD accurately, and its sensitivity limit is around 10 −4 –10 −5 ( Table 1 ) ( 4 , 13 ). The expertise includes not only the technique but also the selection of the right antibody panel, standardized flow data analysis, and extensive knowledge about normal bone marrow (BM) expression patterns of the selected cluster of differentiation (CD) markers.…”

Consolidation: Autologous Stem Cell Transplantation in Acute Leukemia

“…Decision-making might benefit from taking minimal residual disease (MRD) into account [22,23]. Real-time quantitative PCR (qPCR) and multiparameter flow cytometry (MFC) are effective techniques for monitoring MRD before and after ASCT in patients with AML, and MRD status pre-ASCT is an independent prognostic factor for both OS and LFS after ASCT [24,25]. Whereby MRD-negative patients may be consolidated by ASCT and MRD-positive patients may proceed to allo-SCT.…”